Project Summary Oxidation reactions exhibit significant value in the synthesis of pharmaceuticals, natural products and other bioactive compounds, since they often facilitate the introduction of heteroatoms into these molecules. The majority of methods for performing oxidation reactions rely on undesirable oxidants that generate stoichiometric waste, which often limits their use in large-scale applications (e.g., process-scale pharmaceutical synthesis). In contrast, Nature widely uses the most abundant oxidant, O2, in selective oxidation reactions. Many oxygenases and oxidases feature redox-active organic (co)catalysts, such as quinones and tyrosyl radicals, in the active site of the enzyme. In the proposed work, we will develop reactions catalyzed by three bioinspired classes of redox-active (co)catalysts for synthetic oxidation reactions: (1) quinone catalysts for oxidative dehydrogenation and oxidative coupling reactions of amines and other substrates, (2) nitroxyl radical (co)catalysts for oxidative coupling reactions, and enantio-, diastereo-, and chemoselective oxidations of alcohols, and (3) imidoxyl radical (co)catalysts for oxidative conversion of activated C?H bonds into C?N, C?O, and other C?X bonds. The quinone-catalyzed reactions will facilitate dehydrogenation and oxidative coupling reactions of N-heterocycles, which are present in >50% of small-molecule drugs. The Cu/nitroxyl chemistry will be used to achieve versatile oxidative coupling reactions to generate amides, carbamates, and ureas as well as site-selective alcohol oxidation in complex molecules, including late-stage functionalization of natural products and pharmaceuticals. The imidoxyl radical chemistry will exploit the utility of electrochemical methods to overcome intrinsic limitations identified in prior studies and will provide the basis for selective generation of carbon-based radicals that can undergo subsequent functionalization. In each of these project areas, empirical reaction discovery efforts will be complemented by holistic mechanistic studies of the catalytic mechanisms and redox behavior of the (co)catalysts.